Physically realistic homology models built with ROSETTA can be more accurate than their templates

TitlePhysically realistic homology models built with ROSETTA can be more accurate than their templates
Publication TypeJournal Article
Year of Publication2006
AuthorsMisura, K. M. S., Chivian D., Rohl C. A., Kim D. E., & Baker D.
JournalProceedings of the National Academy of Sciences of the United States of America
Volume103
Issue14
Pagination5361-6
Date Published2006 Apr 4
ISSN0027-8424
KeywordsModels, Theoretical, Primary Publication, Protein Folding, Proteins
Abstract

We have developed a method that combines the ROSETTA de novo protein folding and refinement protocol with distance constraints derived from homologous structures to build homology models that are frequently more accurate than their templates. We test this method by building complete-chain models for a benchmark set of 22 proteins, each with 1 or 2 candidate templates, for a total of 39 test cases. We use structure-based and sequence-based alignments for each of the test cases. All atoms, including hydrogens, are represented explicitly. The resulting models contain approximately the same number of atomic overlaps as experimentally determined crystal structures and maintain good stereochemistry. The most accurate models can be identified by their energies, and in 22 of 39 cases a model that is more accurate than the template over aligned regions is one of the 10 lowest-energy models.

Alternate JournalProc. Natl. Acad. Sci. U.S.A.
AttachmentSize
misura06A.pdf2.12 MB